Prenatal Phenotypic Features of Five Fetal Cases With RNU4ATAC-Associated Microcephalic Osteodysplastic Primordial Dwarfism Type I.

Biallelic variants in the non-coding gene RNU4ATAC, which encodes a minor spliceosome small nuclear RNA, cause MOPD1; because the gene is non-coding, detection requires genome sequencing or a targeted approach, as standard exome sequencing may miss them.

This retrospective case series reports prenatal sonographic features, genomic findings and pregnancy outcomes of five fetuses with biallelic pathogenic RNU4ATAC variants causing MOPD1. Diagnoses were made by prenatal ultrasound and confirmed by genome sequencing or targeted exome sequencing, either prenatally or after termination of pregnancy. All fetuses showed consistent anomalies: intrauterine growth restriction, microcephaly, agenesis of the corpus callosum, intracranial cysts, lissencephaly and micrognathia, with growth restriction the earliest finding in all five cases. Features suggestive of skeletal dysplasia were identified in only one case. Termination of pregnancy was chosen in four cases; the fifth fetus was delivered at 39+1 weeks with the genetic diagnosis confirmed at 27 weeks.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The key point for prenatal diagnosis is the mismatch between the disease name and what ultrasound actually shows: skeletal dysplasia was present in only one of five cases, whereas the combination of early growth restriction, microcephaly and corpus callosum agenesis was constant and detectable around 18 weeks. The second message is technical and directly actionable in the laboratory: because RNU4ATAC is non-coding, it escapes standard exome analysis, which justifies planning a genome or a panel explicitly covering small nuclear RNAs in this presentation. With only five cases and no denominator, the series informs neither the frequency nor the positive predictive value of this sonographic triad.

Analysis by Dr Thibaut Benquey